Spray-Dried Proliposome Microparticles for High-Performance Aerosol Delivery Using a Monodose Powder Inhaler

Proliposome formulations containing salbutamol sulphate (SS) were developed using spray drying, and the effects of carrier type (lactose monohydrate (LMH) or mannitol) and lipid to carrier ratio were evaluated. The lipid phase comprised soy phosphatidylcholine (SPC) and cholesterol (1:1), and the ratios of lipid to carrier were 1:2, 1:4, 1:6, 1:8 or 1:10 w/w. X-ray powder diffraction (XRPD) revealed an interaction between the components of the proliposome particles, and scanning electron microscopy (SEM) showed that mannitol-based proliposomes were uniformly sized and spherical, whilst LMH-based proliposomes were irregular and relatively large. Using a two-stage impinger (TSI), fine particle fraction (FPF) values of the proliposomes were higher for mannitol-based formulations, reaching 52.6%, which was attributed to the better flow properties when mannitol was used as carrier. Following hydration of proliposomes, transmission electron microscopy (TEM) demonstrated that vesicles generated from mannitol-based formulations were oligolamellar, whilst LMH-based proliposomes generated ‘worm-like’ structures and vesicle clusters. Vesicle size decreased upon increasing carrier to lipid ratio, and the zeta potential values were negative. Drug entrapment efficiency (EE) was higher for liposomes generated from LMH-based proliposomes, reaching 37.76% when 1:2 lipid to carrier ratio was used. The in vitro drug release profile was similar for both carriers when 1:6 lipid to carrier ratio was used. This study showed that spray drying can produce inhalable proliposome microparticles that can generate liposomes upon contact with an aqueous phase, and the FPF of proliposomes and the EE offered by liposomes were formulation-dependent

Exploring formalized elite coach mentoring programmes in the UK: ‘We’ve had to play the game’

Formalized mentoring programmes have been implemented increasingly have been implemented by UK sporting institutions as a central coach development tool, yet claims supporting formal mentoring as an effective learning strategy are often speculative, scarce, ill-defined and accepted without verification. The aim of this study, therefore, was to explore some of the realities of formalized elite sports coaching mentoring programmes. Data were collected using semi-structured interviews with 15 mentors of elite coaches on formal programmes, across a range of sports. The findings were read through a Bourdieusian lens and revealed the importance of understanding the complexities of elite sports coaching environments, that elite sports coach development is highly specific and, therefore, should not be over-formalized, and how current elite sport coach mentoring programmes may be better conceptualized as a form of social control rather than being driven by pedagogical concerns. Following this empirically based analysis of practice, a number of implications for Governing Bodies (GBs), mentors and mentees were considered

An analysis of the value of multiple mentors in formalised elite coach mentoring programmes

Background: Within the context of sports coaching and coach education, formalised mentoring relationships are often depicted as a mentor–mentee dyad. Thus, mentoring within sports coaching is typically conceptualised as a one-dimensional relationship, where the mentor is seen as the powerful member of the dyad, with greater age and/or experience (Colley 2003). Aim: The aim of this study was to explore the concept of a multiple mentor system in an attempt to advance our theoretical and empirical understanding of sports coach mentoring. In doing so, this paper builds upon the suggestion of Jones, Harris and Miles (2009) who highlight the importance of generating empirical research to explore current mentoring approaches in sport, which in turn can inform meaningful formal coach education enhancement. The significance of this work therefore lies in opening up both a practical and a theoretical space for dialogue within sports coach education in order to challenge the traditional dyadic conceptualisation of mentoring and move towards an understanding of ‘mentoring in practice’. Method: Drawing upon Kram’s (1985) foundational mentoring theory to underpin a multiple mentoring support system, 15 elite coach mentors across a range of sports were interviewed in an attempt to explore their mentoring experiences. Subsequently, an inductive thematic analysis endeavoured to further investigate the realities and practicalities of employing a multiple mentoring system in the context of elite coach development. Results: The participants advocated support for the utilisation of a multiple mentor system to address some of the inherent problems and complexities within elite sports coaching mentoring. Specifically, the results suggested that mentees sourced different mentors for specific knowledge acquisition, skills and attributes. For example, within a multiple mentor approach, mentors recommended that mentees use a variety of mentors, including cross-sports and non-sport mentors. Conclusion: Tentative recommendations for the future employment of a multiple mentoring framework were considered, with particular reference to cross-sports or non-sport mentoring experiences

WS-PGRADE workflows for cloud-based distributed simulation

Modeling and Simulation (M&S) is used for systems analysis and decision making in existing or new systems. Modeling large and complex organizations produces large-scale simulations that are difficult or impossible to run on a single computer. Such experiment execution requires high computation. Distributed Simulation (DS) allows modeling of large systems as smaller submodels that execute on different nodes of a computer network and interoperate with each other in order to compose larger systems. Furthermore, cloud computing offers on-demand access to multiple compute resources. Consequently, being able to run DS on cloud resources allows for more experimentation with large-scale simulations in a cost-effective way. However, deploying DS and in fact Cloud-based DS presents significant technical challenges. This paper proposes a framework for deploying DS on the cloud in a transparent manner using the CloudSME Simulation Platform based on WS-PGRADE workflows. A healthcare case study is used to demonstrate our approach.Special thanks to Dr. Tamas Kiss and Mr Hannu Visti, Centre for Parallel Computing, University of Westminster for supporting in this study

Genomic and phenotypic analyses of recent Acinetobacter baumannii isolates from tertiary care hospitals in Thailand

Antibiotic resistant strains of Acinetobacter baumannii are responsible for a large and increasing burden of nosocomial infections in Thailand and other countries of Southeast Asia. New approaches to their control and treatment are urgently needed and we are actively seeking biological agents that remove the polysaccharide capsules that protect these pathogens from the host’s immune system. To examine phylogenetic relationships, distribution of capsule chemotypes, acquired antibiotic resistance determinants, susceptibility to complement and other traits associated with systemic infection, we sequenced 191 recent isolates from three tertiary referral hospitals in Thailand and used phenotypic assays to characterise key aspects of infectivity. Several distinct lineages were circulating in three hospitals and the majority belonged to global clonal group 2 (GC2). Very high levels of resistance to carbapenems and other front-line antibiotics were found, as were a number of widespread plasmid replicons. A high diversity of capsule genotypes were encountered with only three (KL6, KL10 and KL47) above 10% frequency. Almost 90% of GC2 isolates belonged to the most common capsule genotypes and were fully resistant to the bactericidal action of human serum complement; we attribute this trait to the presence of a substantial protective capsule and for this to represent a key determinant of virulence for systemic infection. We conclude that current Thai nosocomial isolates represent potential targets for therapeutic strategies designed to remove the polysaccharide capsule from extensively drug-resistant A. baumanii during the course of systemic infection

Step towards monitoring intelligent agents in healthcare information systems

A platform for establishing interoperability between heterogeneous information systems implemented in a hospital environment is more a requirement than an option. The Agency for the Integration, Diffusion and Archiving of Medical and Clinical Information (AIDA) is an interoperability platform designed specifically to address the problem of integrating information from multiple systems and addressing interoperability, confidentiality, integrity and data availability. This article focuses on the relevance and need for such vigilance, finding and designing effective new ways to establish them. This study culminated in the creation of AIDAMonit, a surveillance platform developed and tested by ALGORITMI Center researchers, which has shown promise and is extremely beneficial for the well-functioning of the health facilities currently using the AIDA platform.This work has been supported by FCT – Fundação para a Ciência e Tecnologia within the Project Scope: UID/CEC/00319/2019 and DSAIPA/DS/0084/2018

Digital PCR methods improve detection sensitivity and measurement precision of low abundance mtDNA deletions

Mitochondrial DNA (mtDNA) mutations are a common cause of primary mitochondrial disorders, and have also been implicated in a broad collection of conditions, including aging, neurodegeneration, and cancer. Prevalent among these pathogenic variants are mtDNA deletions, which show a strong bias for the loss of sequence in the major arc between, but not including, the heavy and light strand origins of replication. Because individual mtDNA deletions can accumulate focally, occur with multiple mixed breakpoints, and in the presence of normal mtDNA sequences, methods that detect broad-spectrum mutations with enhanced sensitivity and limited costs have both research and clinical applications. In this study, we evaluated semi-quantitative and digital PCR-based methods of mtDNA deletion detection using double-stranded reference templates or biological samples. Our aim was to describe key experimental assay parameters that will enable the analysis of low levels or small differences in mtDNA deletion load during disease progression, with limited false-positive detection. We determined that the digital PCR method significantly improved mtDNA deletion detection sensitivity through absolute quantitation, improved precision and reduced assay standard error